The Innovative Medicines Initiative (IMI) is the result of a partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA). This organization aims to promote the open sharing of knowledge and expertise between academia and industry, and will support such research leading to the development of more effective and safer medical treatments for patients. IMI launched its first two projects on February 11th 2013. They focus on bacterial resistance to antibiotics, a problem of ever greater concern worldwide, with the spread of multidrug resistance (MDR). SOLEIL is involved in one of these projects named "TRANSLOCATION."
Antimicrobial resistance (AMR) is responsible for approximately 25,000 deaths each year in Europe, and the economic cost is estimated at 1.5 billion euros. "Antibiotic resistance is becoming a public health emergency of yet unknown proportions", according to the World Health Organization, so large-scale action is required. Hence the "New Drugs for Bad Bugs (ND4BB)" initiative, an unprecedented partnership between academic and industrial organizations supported by IMI, an organization funded equally by the EU and EFPIA.
Two projects, "COMBACTE" (Combatting Bacterial Resistance in Europe) and "TRANSLOCATION" (molecular basis of the bacterial cell wall permeability) form part of this ND4BB program. They bring together large companies, but also specialists in the biotechnology and biopharmaceutical fields, universities, hospitals, foundations and patients associations throughout Europe.
TRANSLOCATION: circumventing the "tricks" of resistant bacteria
Resistant bacteria develop ways of protecting themselves against antibiotics, including expelling harmful molecules through efflux pumps: if the drug’s active ingredient does not reach a sufficiently high concentration in the bacteria to block its target, it will not be destroyed. The aim of the TRANSLOCATION program is to molecularly and genetically dissect, prevent and control this type of protection mechanism.
SOLEIL is involved in this project, more specifically with the DISCO beamline, and has been welcoming groups working in this field over the last few years.
The ongoing collaboration between DISCO and UMR-MD1 (Aix-Marseille University, AMU-IRBA) has clearly shown that the concentration of antibiotics in bacteria is related to the activity of certain resistance mechanisms; the heterogeneity detected in bacterial populations would be responsible for the selection and spread of individuals with antimicrobial resistance.
Image of an Enterogenes aerobacter bacterium (transmission electronic microscopy)© JM Pagès.
These studies will continue as part of the TRANSLOCATION program to determine the relationship between the structure and concentration of the antibiotic and its localization in bacteria and to clarify the role of membrane permeability in the accumulation of antibiotic sensitivity in resistant bacteria. The goal is to decipher, using single-cell resolution, the genetic/molecular events that control this antibiotic accumulation and in the longer term to knockout these mechanisms in order to restore the antibiotic action.
Partners involved in the TRANSLOCATION project include AMU-IRBA, AP-HP, CNRS, INSERM, Universities in Spain, Germany, United Kingdom, Ireland, Italy and Switzerland, as well as several companies such as GSK, AstraZeneca and Sanofi-Aventis.